Clinical Trials /

A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

NCT04657224

Description:

The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination in different histologies/participant populations (Part B - Cohort Expansion).

Related Conditions:
  • B-Cell Non-Hodgkin Lymphoma
  • Chronic Lymphocytic Leukemia
Recruiting Status:

Recruiting

Phase:

Phase 1

Trial Eligibility

Document

Title

  • Brief Title: A Study of JNJ-64264681 and JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia
  • Official Title: A Phase 1b, Open-Label Study of the Safety, Pharmacokinetics, and Pharmacodynamics of JNJ-64264681 in Combination With JNJ-67856633 in Participants With Non-Hodgkin Lymphoma and Chronic Lymphocytic Leukemia

Clinical Trial IDs

  • ORG STUDY ID: CR108877
  • SECONDARY ID: 2020-003149-12
  • SECONDARY ID: 64264681LYM1002
  • NCT ID: NCT04657224

Conditions

  • Lymphoma, Non-Hodgkin
  • Chronic Lymphocytic Leukemia

Interventions

DrugSynonymsArms
JNJ-64264681Part A: Dose escalation: JNJ-64264681 and JNJ-67856633
JNJ-67856633Part A: Dose escalation: JNJ-64264681 and JNJ-67856633

Purpose

The primary purpose of this study is to determine: the recommended Phase 2 doses (RP2Ds) of JNJ-64264681 and JNJ 67856633 when administered together in participants with B cell non-Hodgkin lymphoma (NHL) and chronic lymphocytic leukemia (CLL) (Part A - Dose Escalation); and the safety of the RP2Ds for this combination in different histologies/participant populations (Part B - Cohort Expansion).

Detailed Description

      Bruton's tyrosine kinase (BTK) is a cytoplasmic tyrosine kinase that plays a critical role in
      B cell activation via the B cell receptor (BCR) signaling pathway. BTK is important for
      normal B-cell activation and the pathophysiology of B cell malignancies. A few BTK inhibitors
      have demonstrated clinical activity in non-Hodgkin lymphoma (NHL) and chronic lymphocytic
      leukemia (CLL). Non-Hodgkin lymphoma represents a diverse set of diseases, of which more than
      60 subtypes have been identified and classified by the world health organization.
      JNJ-64264681 is a second-generation, orally active, selective, and irreversible covalent
      inhibitor of BTK and JNJ-67856633 is an orally bioavailable, potent, and selective first in
      class mucosa-associated lymphoid tissue lymphoma translocation protein 1 (MALT1) inhibitor
      that binds to an allosteric site on MALT1 with a mixed-type mechanism. JNJ-64264681 and
      JNJ-67856633 inhibit BTK and MALT1, respectively, and both BTK and MALT1 are involved in
      transmitting the pro-survival BCR signal. The study will consist of Screening Phase (28
      days); Treatment Phase (from Cycle 1 Day 1 up to end of treatment, each cycle is a 21-day
      cycle) and a Follow-up Phase (from end of treatment visit until lost to follow-up, withdrawal
      of consent, death, 6 months after start of first subsequent antineoplastic therapy). The
      total study duration is estimated at 2 years and 2 months. Safety assessments will include
      physical examinations, vital signs, electrocardiograms, clinical safety laboratory
      assessments, eastern cooperative oncology group performance status, echocardiogram and
      adverse events monitoring.
    

Trial Arms

NameTypeDescriptionInterventions
Part A: Dose escalation: JNJ-64264681 and JNJ-67856633ExperimentalParticipants will receive JNJ-64264681 and JNJ-67856633 will be administered together until disease progression, intolerable toxicity, withdrawal of consent, or the investigator.
  • JNJ-64264681
  • JNJ-67856633
Part B: Cohort Expansion: JNJ-64264681 and JNJ-67856633ExperimentalParticipants will receive JNJ-64264681 and JNJ-67856633 at the recommended Phase 2 dose (RP2D) determined in Part 1.
  • JNJ-64264681
  • JNJ-67856633

Eligibility Criteria

        Inclusion Criteria:

          -  Eastern Cooperative Oncology Group (ECOG) performance status grade of 0 or 1

          -  Cardiac parameters within the following range: corrected QT interval (QTcF) <= 480
             milliseconds

          -  Participants with B cell non-Hodgkin lymphoma (NHL) must have tumor tissue available
             at baseline as described in the protocol. This is not required for participants with
             chronic lymphocytic leukemia (CLL)

          -  Women of childbearing potential must agree to use a barrier method of contraception;
             use a highly effective preferably user-independent method of contraception; not to
             donate eggs (ova, oocytes) or freeze them for future use for the purposes of assisted
             reproduction during the study; not to plan to become pregnant; and not to breast-feed

        Exclusion Criteria:

          -  Part A and select cohorts in Part B: Prior treatment with JNJ 64264681 or
             JNJ-67856633. Previously discontinued treatment with a Bruton's tyrosine kinase (BTK)
             or mucosa-associated lymphoid tissue lymphoma translocation protein (MALT) inhibitor
             other than JNJ 64264681 or JNJ-67856633 due to participant or doctor choice without
             evidence of progression or intolerable class-related toxicity will be eligible

          -  Known (active) central nervous system (CNS) involvement

          -  Received prior solid organ transplantation

          -  Participant has known allergies, hypersensitivity, or intolerance to JNJ-64264681 or
             JNJ 67856633 or excipients

          -  Toxicities from previous anti-cancer therapies that have not resolved to baseline
             levels, or to Grade less than (<) 2 (except for alopecia [>=Grade 2], vitiligo [Grade
             2] and peripheral neuropathy [Grade 1])
      
Maximum Eligible Age:N/A
Minimum Eligible Age:18 Years
Eligible Gender:All
Healthy Volunteers:No

Primary Outcome Measures

Measure:Part A: Number of Participants with Dose-limiting Toxicity (DLT)
Time Frame:Up to 21 days
Safety Issue:
Description:Number of participants with DLT will be assessed. The DLTs are specific adverse events and are defined as any of the following: high grade non-hematologic toxicity, or hematologic toxicity.

Secondary Outcome Measures

Measure:Plasma Concentrations of JNJ-64264681 and JNJ-67856633
Time Frame:Up to 2 years and 3 months
Safety Issue:
Description:Plasma concentrations of JNJ-64264681 and JNJ-67856633 will be assessed.
Measure:Bruton's Tyrosine Kinase (BTK) Occupancy in Peripheral Blood Mononuclear Cell (PBMCs)
Time Frame:Up to 2 years and 3 months
Safety Issue:
Description:BTK occupancy will be assessed.
Measure:Biological Activity of JNJ-67856633
Time Frame:Up to 2 years and 3 months
Safety Issue:
Description:Biological activity of JNJ-67856633 as measured by NF-kB assay will be assessed.
Measure:Overall Response Rate (ORR)
Time Frame:Up to 2 years and 3 months
Safety Issue:
Description:ORR is defined according to Non-Hodgkin Lymphoma, International Workshop on Chronic Lymphocytic Leukemia (iwCLL); and Response assessment in Waldenström Macroglobulinemia (IWWM).
Measure:Time to First Response
Time Frame:Up to 2 years and 3 months
Safety Issue:
Description:Time to first response defined for the responders as the time from the date of first dose of study treatment to the date of initial documentation of a first response as defined in the disease-specific response criteria.
Measure:Duration of Response
Time Frame:Up to 2 years and 3 months
Safety Issue:
Description:DOR will be calculated from the date of initial documentation of a response to the date of first documented evidence of relapse, as defined in the disease-specific response criteria, or death due to any cause, whichever occurs first.

Details

Phase:Phase 1
Primary Purpose:Interventional
Overall Status:Recruiting
Lead Sponsor:Janssen Research & Development, LLC

Last Updated

April 23, 2021